Frontiers in Pharmacology
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2022
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IF 5.988
Shi Le,Shu Yang,Hu Xiangdong,Akram Waheed,Wang Jun,Dong Shuang,Luo Biaobiao,Zhang Jiuliang,Hu Sheng,Li Xiaohua,Hu Xuebo
Chemotherapy is considered a most effective way to treat cancer. However, it is very common that chemotherapy causes unbearable mental and physical side effects to cancer patients, which ultimately reduces the patients’ confidence of overcoming diseases and compromises the treatment of chemotherapy. Cisplatin (DDP), a widely used anticancer agent for various types of cancers, also damages nontumor cells and tissues, which are mostly related to the activation of the inflammation pathway. Previously, we have discovered a few rational formulas of food as medicine materials that reduced systemic inflammation in in vitro and in vivo models. Hence, this study reports the ability of an optimized traditional Chinese anti-inflammatory formulation capable of synergizing the antitumor effect of DDP in vitro and in vivo. More significantly, by formulation of two anti-inflammatory herbal medicine, the Chrysanthemum × morifolium (Ramat.) Hemsl [Asteraceae] and Lonicera japonica Thunb [Caprifoliaceae] with a mediator Glycyrrhiza uralensis Fisch. ex DC [Fabaceae], a best formula relieved the kidney damage imposed by DDP. Treatments of various combinations of major chemical components of the three herbs also exhibited a similar trend for lowering the DDP-induced nephrotoxicity; however, contrary to that of the formula of herbal extracts, all chemical formulas could not recover the body weight and food intake of the tumor-bearing mice treated by DDP. Our findings suggested that the therapeutic index of DDP-based chemotherapy was able to be improved by minimizing toxicities from the two-herb formula to inhibit the inflammation in mouse tumor models and DDP-induced acute kidney injury mouse models.
研究领域:
肿瘤学
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药理学
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中医药学
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分子生物学
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DOI
PubMed
高影响因子
Thoracic Cancer
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2020
·Vol. 11
·期 11
·3365-3374
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IF 2.61
Qi Zhang,Qingxin Cui
Background One classic traditional Chinese medicine theory is that the “lung and intestine are exterior-interiorly related”; however, this has not been confirmed experimentally. The aim of this study was to provide a biological basis for the theory by measuring the tissue distribution of andrographolide. Methods Acute pneumonia was induced in a mouse model by repeated stimulation with lipopolysaccharide. The distribution of andrographolide in mice was observed by positron emission tomography (PET) imaging with [ 18 F]-labeled andrographolide, and changes in the in vivo distribution before and after modeling were compared. Subsequently, the consistency of pathological changes in lung and intestine was confirmed by observation of pathological sections. Finally, the results were verified by cytokine detection. Results The value of organ uptake, pathological changes and inflammatory factor expression of the lung and intestine were consistent. The concentration of andrographolide in the lung and intestine increased significantly, and was confirmed by pathology and enzyme-linked immunosorbent assays (ELISA). Conclusions Micro-positron emission tomography (microPET) can be used to visually observe the distribution of medicinal ingredients in vivo, and [ 18 F]-andrographolide can be used as a tool to assess the interior-exterior relationship between the lung and intestine.
研究领域:
药理学
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医学
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影像科学
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中医药学
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产品关联
DOI
PubMed
高影响因子
Computational and Mathematical Methods in Medicine
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2022
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IF 2.809
Zhulin Wu,Jianyuan Kang,Wanjun Tan,Chunshan Wei,Li He,Xiaoyan Jiang,Lisheng Peng
Objective. Traditional Chinese medicine (TCM) is an important part of the comprehensive treatment of hepatocellular carcinoma (HCC), and Chinese materia medica formulas with the effect of “Yiqi Jianpi” (replenishing qi and strengthening spleen) or “Jiedu” (removing toxicity) have been proved to be effective in treating HCC. However, mechanisms of these formulas in treating HCC remain unclear. In this paper, our goal is to explore the antitumor activity and its molecular mechanisms of Yiqi Jianpi Jiedu (YQJPJD) formula against HCC. Methods. The bioactive ingredients and targets of YQJPJD formula and HCC targets were screened by five Chinese materia medicas and two disease databases, respectively. The network pharmacology was utilized to construct the relationship network between YQJPJD formula and HCC, and the mechanisms were predicted by the protein-protein interaction (PPI) network, pathway enrichment analysis, bioinformatics, and molecular docking. Numerous in vitro assays were performed to verify the effect of YQJPJD formula on HCC cells, cancer-associated targets, and PI3K/Akt pathway. Results. The network relationship between YQJPJD formula and HCC suggested that YQJPJD formula mainly regulated the potential therapeutic targets of HCC by several key bioactive ingredients (e.g., quercetin, luteolin, baicalein, and wogonin). PPI network, bioinformatics, and molecular docking analyses displayed that YQJPJD formula may play an anti-HCC effect through key targets such as MAPK3, RAC1, and RHOA. Additionally, pathway analysis demonstrated that YQJPJD formula could play an anti-HCC effect via multiple pathways (e.g., PI3K-Akt and hepatitis B). Experimental results showed that YQJPJD formula could effectively inhibit the proliferation, migration, and invasion of HCC cells and promote HCC cell apoptosis in a concentration-dependent manner. Moreover, YQJPJD formula could decrease the mRNA expression of β-catenin, MAPK3, and RHOA and the protein expression of phosphorylated PI3K and Akt. Conclusion. YQJPJD formula mainly exerts its anti-HCC effect through multiple bioactive ingredients represented by quercetin, as well as multiple pathways and targets represented by PI3K/Akt pathway, β-catenin, MAPK3, and RHOA.
研究领域:
药理学
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肿瘤学
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中医药
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
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2025
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IF 13
Lin-Tao Xu,Qing-Tong Han,Zhen-Peng Xu,Xiao-Ning Wang,Hua Zhang,Tao Shen
Introduction Chronic obstructive pulmonary disease (COPD) represents a significant global health challenge, characterized by substantial morbidity and mortality rates. In traditional Chinese medicine (TCM), Farfarae Flos (FF) has been widely utilized as a therapeutic agent for COPD. However, its specific bioactive compounds and the underlying mechanisms are unclear. Objectives This study aims to identify bioactive constituent of FF against COPD and illustrate its therapeutic target and mechanism. Methods and Results In this research, a high-throughput screening on constituents of FF was conducted, leading to the identification of a potent anti-COPD lead, tussilagone (TUS). Utilizing biotin-labeling approach, Kelch-like ECH-associated protein 1 (KEAP1), the ubiquitin E3 ligase of nuclear factor erythroid 2-related factor 2 (Nrf2), was identified to be the direct target of TUS. Mechanistically, TUS activated KEAP1-Nrf2 axis by covalent modification of cysteine 434 (Cys434), a novel high-reactivity cysteine of KEAP1. TUS-mediated Nrf2 activation further suppressed the activation of nuclear factor kappa-B (NF-κB) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, consequently attenuating lung inflammation in COPD. Conclusion TUS was identified as the bioactive constituent of FF against COPD, which directly targeted Cys434 of KEAP1. KEAP1 was proven to be a pharmacological target for the treatment of COPD, and Cys434 was identified to be the first highly reactive cysteine in Kelch domain of KEAP1. TUS inhibits lung inflammation by regulating Nrf2 and NF-κB/NLRP3, which is the mechanism of FF against COPD
研究领域:
药理学
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分子生物学
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呼吸医学
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民族药理学
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生物化学
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免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Yu Wang,Zhi-jian Lin,Jing Huang,Meng-zhen Chu,Xue-li Ding,Wen-jing Li,Qiu-yue Mao,Bing Zhang
Ethnopharmacological relevance Shenling Baizhu San (SLBZ) is a famous Traditional Chinese Medicine (TCM) formula that strengthens the spleen for replenishing qi, removing dampness, and inducing diuresis to relieve diarrhea. Combining the TCM interpretation that dampness is a vital pathogenesis factor in hyperuricemia occurrence and development, SLBZ has excellent potential against hyperuricemia from the perspective of TCM theories. Aim of the study This study aimed to investigate the efficacy of SLBZ against hyperuricemia and its possible mechanism with emphasis on the active components and the core targets. Materials and methods In the present study, we employed meta-analysis and a hyperuricemia quail model to evaluate the uric acid-lowering effect of SLBZ. Bodyweight, serum uric acid , and excreta uric acid levels in quails were assessed. Subsequently, we analyzed the potential active components and core targets of SLBZ against hyperuricemia by network pharmacology and calculated their interaction using molecular docking. Furthermore, the hyperuricemia rats treated with interfering agents of core targets were established to determine the central role of selected targets in hyperuricemia progression. Besides, we isolated and characterized the primary renal tubular epithelial cells of quails to verify the active components and core targets of SLBZ against hyperuricemia. Western blotting was used to observe the expression of core targets treated with active components under the stimulation of interfering agents. Results Data from meta-analysis and animal experiments showed that SLBZ could work effectively against hyperuricemia. Hyperuricemia quails treated with SLBZ displayed significantly reduced serum uric acid levels accompanied by increased excretion of uric acid. According to network pharmacology and molecular docking results, 34 potential active components and the core target peroxisome proliferator-activated receptor gamma (PPARγ) for SLBZ against hyperuricemia were identified. The decreased serum uric acid levels in hyperuricemia rats treated with rosiglitazone , an agonist of PPARγ, confirms the essential role of PPARγ in the pathological process of hyperuricemia. Moreover, we first successfully isolated and characterized the primary renal tubular epithelial cells of quails and observed enhanced phosphorylation of PPARγ at Ser273 in cells handled with high-level uric acid. Whereas, the enhanced expression of p-PPARγ Ser273 could be down-regulated by luteolin and naringenin , two active components of SLBZ against hyperuricemia. Conclusion In summary, SLBZ is a promising anti-hyperuricemia agent, and luteolin and naringenin are the active components for SLBZ against hyperuricemia by down-regulating phosphorylation of PPARγ at Ser273.
研究领域:
药理学
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民族药理学
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网络药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Small
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2024
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IF 13
Jialu Zhuang,Hao Zhang,Jin Wu,Danyou Hu,Tao Meng,Jing Xue,Hanyang Xu,Gang Wang,Hua Wang,Guiyang Zhang
The escalating misuse of antipyretic and analgesic drugs, alongside the rising incidents of acute drug-induced liver injury, underscores the need for a precisely targeted drug delivery system. Herein, two isoreticular covalent organic frameworks (Se-COF and Se-BCOF) are developed by Schiff-base condensation of emissive tetraphenylethylene and diselenide-bridged monomers. Leveraging the specific affinity of macrophages for mannose, the first precise targeting of these COFs to liver macrophages is achieved. The correlation is also explored between the therapeutic effects of COFs and the NLRP3/ASC/Caspase-1 signaling pathway. Utilizing this innovative delivery vehicle, the synergistic delivery of matrine and berberine are accomplished, compounds extracted from traditional Chinese medicine. This approach not only demonstrated the synergistic effects of the drugs but also mitigated their toxicity. Notably, berberine, through phosphorylation of JNK and up-regulation of nuclear Nrf-2 and its downstream gene Mn-SOD expression, simultaneously countered excessive ROS and suppressed the activation of the NLRP3/ASC/Caspase-1 signaling pathway in injured liver tissues. This multifaceted approach proved highly effective in safeguarding against acute drug-induced liver injury, ultimately restoring liver health to normalcy. These findings present a novel and promising strategy for the treatment of acute drug-induced liver injury.
研究领域:
药学
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材料科学
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肝病学
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免疫学
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中医药
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
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IF 5.3
Hao Cui,Yanchi Liu,Ying Yu,Dong Lv,Sha Ma,Mingju Gao,Ye Yang,Cheng Yuan,Yuan Liu,Chengxiao Wang
In this study, we aimed to develop brain-targeted co-delivery liposomes for the concurrent delivery of Panax notoginseng saponins (PNS) and acetylsalicylic acid (ASA) for the treatment of ischemic stroke. Within this system, PNS served as a cholesterol substitute, integrating into the phospholipid bilayer of the liposomes, while ASA was encapsulated internally. A poly-2-methacryloyloxyethyl phosphorylcholine (PMPC) polymer was synthesized and incorporated into the liposome surface. This formulation demonstrated an enhanced PNS-loading capacity and facilitated the synchronized delivery of key saponin components. Following PMPC modification, the liposomes exhibited prolonged circulation and improved transport across the blood–brain barrier (BBB) through acetylcholine receptor-mediated pathways. Furthermore, the co-delivery system exhibited enhanced therapeutic efficacy in a rat model of cerebral ischemia–reperfusion injury via the phosphoinositide 3-kinase/protein kinase C pathway. Additional analyses revealed significant effects on the metabolism of neurotransmitters, amino acids, folate, and various other pathways, indicating a multi-faceted therapeutic effect. Overall, this study presents an innovative research strategy for the comprehensive delivery of diverse components in traditional Chinese medicine formulations, highlighting the potential for synergistic treatments that combine traditional Chinese medicine with chemical agents.
研究领域:
药学
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神经科学
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中医药
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药物递送系统
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中风治疗
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产品关联
DOI
PubMed
高影响因子
IUBMB LIFE
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2024
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IF 3.7
Yexuan Lin,Na Sun,Dengyuan Liu,Xinmeng Yang,Yixin Dong,Chengyu Jiang
In 2020, the number of deaths caused by lung cancer worldwide reached 1,796,144, making it the leading cause of cancer-related deaths. Cyclooxygenase-2/prostaglandin endoperoxide synthase 2 ( COX-2/PTGS2 ) is overexpressed in lung cancer, which promotes tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. Here, we report that the oligonucleotide drug HQi-sRNA-2 from Traditional Chinese Medicine Huangqin targeting COX-2/PTGS2 significantly inhibited proliferation, migration, and invasion and induced apoptosis in the human lung cancer cell line NCI-H460. Oral delivery of HQi-sRNA-2 bencaosomes prolonged survival, reduced tumor burden, and maintained weight in a spontaneous mouse lung cancer model. Compared with paclitaxel, HQi-sRNA-2 may be less toxic and have approximately equal efficacy in reducing tumor burden. Our previous studies reported that herbal small RNAs (sRNAs) are functional medical components. Our data suggest that sphingosine (d18:1)-HQi-sRNA-2 bencaosomes, targeting COX-2/PTGS2 and downregulating the PI3K and AKT signaling pathways, may provide novel therapeutics for lung cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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中医药
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
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2024
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IF 2.3
Huafeng Yang,Hui Liu,Yuan Zheng,Bo Li,Shujing Wang,Jun Zhang,Jiandong Wang
Cornus officinalis total glycosides (COTG) derived from the traditional Chinese medicine Cornus officinalis, is a natural immunosuppressant and has been extensively studied in immunomodulation and immunosuppression. This study aimed to explore the effects of COTG on granulomatous lobular mastitis (GLM) and its associated mechanisms. Compared to the model group, COTG effectively ameliorated histopathological damage to breast tissue, reduced mammary gland suppuration, and enhanced the blood-milk barrier. Additionally, COTG treatment reduced the total number of T cells and B cells in GLM rats, significantly improving clinical indicators such as P-selectin, E-selectin, and intercellular cell adhesion molecule-1. We also observed downregulation of CD28 and B7 expression levels, an upregulation of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) expression, and a significant decrease in inflammatory marker levels in the COTG group. COTG exerts an anti-inflammatory effect in GLM by stimulating CTLA-4, inhibiting the B7-CD28 signaling pathway affecting T cell activation, and promoting the blood-milk barrier. These findings suggest that COTG could be a promising therapeutic option for managing GLM, potentially improving patient outcomes by modulating immune responses and reinforcing the blood-milk barrier.
研究领域:
药理学
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免疫学
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病理学
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中医药
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产品关联
DOI
PubMed
高影响因子
Chinese Medicine
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2024
·Vol. 19
·期 1
·1-16
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IF 5.3
Rao Chang,Hu Ruixue,Hu Yongxin,Jiang Yan,Zou Xu,Tang Huilan,Chen Xing,He Xiaoli,Hu Guang
Background Salvia miltiorrhiza (Danshen, DS) and Radix Paeoniae Rubra (Chishao, CS) herbal pair (DS-CS) is a famous traditional Chinese combination which has been used as antithrombotic formular for centuries. However, there is still lack of sufficient scientific evidence to illustrate its underlying mechanisms. The purpose of this study is to investigate the antithrombotic effects of DS-CS extract in zebrafish and explore its possible mechanism of action. Methods The quality of traditional Chinese medicines DS and CS granules was evaluated using High Performance Liquid Chromatography (HPLC). Subsequently, the therapeutic effect of the DS-CS combination and its components, Salvianolic Acid A (SAA) and Paeoniflorin (PF), in various concentrations on thrombosis was experimentally validated. Moreover, the interaction between DS-CS and the thrombosis disease targets was analyzed through network pharmacology, predicting the potential antithrombotic mechanism of DS-CS. Molecular docking and in vivo zebrafish experiments were conducted to validate the predicted targets, with qRT-PCR utilized for target validation. Results DS-CS exhibited anti-thrombotic effect in zebrafish with concentrations ranging from 25 to 300 μg/mL. The co-administration of PF and SAA at 25 μg/mL each revealed a synergistic antithrombotic effect exceeding that of individual components when contrasted with PHZ treatment. Protein–protein interaction (PPI) analysis identified key genes, including Albumin (ALB), Proto-oncogene tyro-sine-protein kinase Src (SRC), Matrix metalloproteinase-9 (MMP9), Caspase-3 (CASP3), Epidermal growth factor receptor (EGFR), Fibroblast growth factor 2 (FGF2), Vascular endothelial growth factor receptor 2 (KDR), Matrix metalloprotein-ase-2(MMP2), Thrombin (F2), and Coagulation factor Xa (F10), associated with the antithrombotic action of PF and SAA. Furthermore, KEGG pathway analysis indicated involvement of lipid metabolism and atherosclerosis pathways. Molecular docking revealed strong binding of PF and SAA to pivotal hub genes, such as SRC, EGFR, and F10. The experimental findings demonstrated that DS-CS could upregulate the mRNA expression levels of EGFR while inhibiting F10 and SRC mRNA levels, thereby ameliorating thrombotic conditions. Conclusion This research provided valuable insights into the potential mechanisms underlying the antithrombotic activity of DS-CS. Our findings suggested that PF and SAA could be the key active ingredients responsible for this activity. The antithrombotic effects of DS-CS appeared to be mediated through the regulation of mRNA expression of SRC, EGFR, and F10. These results enhanced our understanding of DS-CS's therapeutic potential and lay the groundwork for future studies to further elucidate its mechanisms of action.
研究领域:
药理学
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分子生物学
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中医药
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网络药理学
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斑马鱼模型
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产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
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2024
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IF 5.3
Xiaoyu Zhang,Ruihu Zhang,Rui Li,Jiaxing Zhang,Yuefei Wang,Xin Chai,Yuefei Wang
Gardenia blue (GB), a natural active blue pigment, can be synthesized from iridoid glycosides and primary amino-containing compounds in vivo and in vitro . However, limited studies have reported GB synthetic intermediates, leading to unawareness of the formation mechanism of GB. Here, we reported that GB could be detected in rats′ feces, whose formation was simulated by in vitro reaction of amino acid-rich feces extract from rats and genipin (GP) metabolized from geniposide (GE) through β -glucosidase. Firstly, we proved that 14 amino acids (AAs) detected in rats′ feces containing primary amino groups can react with GP to produce GB. Then, taking histidine (His) as example, we characterized the key intermediates during the reaction process, including basic units genihistidine A (GH-A) and dimers. As an active basic unit, GH-A underwent covalent polymerization to form dimer, which then self-assembled into supramolecular spherical nanoparticles through multiple noncovalent interactions, including hydrogen bonds, π-π interactions, and van der Waals interactions. Our study revealed the formation mechanism of GB and provided insights into the bioavailable form of GE from traditional Chinese medicine in vivo .
研究领域:
化学
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生物化学
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药理学
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中医药
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产品关联
DOI
高影响因子
Journal of Functional Foods
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2024
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IF 3.8
Xiling Wang,Yanan Cheng,Bing Zheng,Yi Chen,Jianhua Xie,Xiaobo Hu,Xiaoting Qin,Jiajun Song,Yue Qiu,Qiang Yu
The traditional ‘nine-steam-nine-bask’ method of Polygonatum cyrtonema Hua (PCH) has been controversial due to nine-cycle requirement. This study employed in vitro digestion to investigate changes in bioactive substances, bioaccessibility, and antioxidant activity of PCH at different steam-bask times. It revealed the correlation between bioactive substances and antioxidant activity in PCH, and validated the ‘nine-steam-nine-bask’ process’s efficacy. In undigested samples, total phenol content (TPC), reducing sugar content (RSC), and DPPH and ABTS activities increased with more cycles, peaking in the nine-cycle sample at 7.627 mg GAE/g DW, 465.333 mg GE/g DW, 17.698, and 36.986 μmol VCE/g DW. Similar trends were observed throughout digestion. Total sugar (755.96 mg GE/g DW) and total saponin content (1.35 mg DE/g DW) plateaued during gastrointestinal digestion. Correlation analysis further revealed close relationships between bioactive substances and antioxidant activity. Multivariate statistical analysis confirmed that nine cycles maximized the distinction between steam-bask and non-steam-bask PCH.
研究领域:
药理学
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食品科学
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中医药
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）